KR101203384B1 - Production of lithium diphenylphosphide - Google Patents

Abstract

The present invention relates to a solution of lithium diphenylyphosphide in a solvent which is more stable than when tetrahydrofuran (THF) is used as the solvent, for example diethoxymethane (DEM). The present invention also provides a method of making them.

Description

Production of lithium diphenyl phosphide {PRODUCTION OF LITHIUM DIPHENYLPHOSPHIDE}

This application claims the application of the provisions of section 119 (e) of US Patent Law No. 61 / 029,273, filed February 15, 2008.

The present invention provides a more stable solvent than tetrahydrofuran (THF) when used as a solvent, for example, a solution of lithium diphenylphosphide (lithium diphenylphosphide) in dimethoxymethane (DEM), And it relates to a production method thereof.

Lithium diphenylphosphide is used commercially, for example to remove hydroxyl groups in organic and inorganic compound synthesis, or as ligand in organometallic catalysts. In general, lithium diphenylphosphide is provided as a solvent in tetrahydrofuran. Although these commercially available solutions, lithium dipalephosphide, can be used in tetrahydrofuran, they are not very stable and are not commercially viable. There is a need for new and stable formulations of diphenylphosphide.

U.S. Patent Application No. 5,866,720 discloses triarylphosphine in which an alkali diaryl phosphide is formed by mixing one or more alkali metals, preferably sodium and potassium, in a biphasic mixture in a dilute anhydrous organic liquid in the presence of molecular hydrogen. Is disclosed.

In order to form cycloalkyldiarylphosphine, at least a portion (or alkali metal diarylphosphide recovered therefrom) and cycloalkyl mesylate or tosylate (recovered therefrom) formed in the aforementioned process tosylate) are mixed together and maintained under appropriate reaction conditions. The post reaction is carried out in the presence of sodium residues from the previous reaction. Performing the post reaction under hydrogen atmosphere will inhibit undesirable side reactions.

It is therefore an object of the present invention to provide a stable solution of diphenylphosphide in a solvent which makes the solution more stable than the solution under THF. It is to be understood that the methods for preparing and using such solutions are also within the scope of the present invention. The solvent preferably comprises an ether and more preferably comprises ethers (eg C ₁ -C ₅ ) with minimal steric hindrance around oxygen. Another preferred solvent is 2-methyltetrahydrofuran (2MeTHF), which has improved stability compared to THF.

SUMMARY OF THE INVENTION

The present invention relates, in part, to a solution comprising lithium diphenylphosphide and a solvent that produces a more stable solution than when the solution composition is tetrahydrofuran. Stability is significantly improved compared to THF formulations when tested under temperature controlled atmospheres at 20 ° C. and 35 ° C. in incubators adjusted to an inert static pressure argon atmosphere for a period of 1 to 4 weeks, preferably 4 weeks. In a preferred embodiment, the solvent comprises an organic solvent or is the organic solvent itself. The solvent preferably contains 1 to 5 carbon organisms, preferably at least one oxygen atom. The solvent may be 2-methyltetrahydrofuran or an ether such as diethyl ether; It is preferred to include dimethoxymethane, and triethylorthoformate. It is noted that the mixed solution of the solvent is within the scope of the present invention.

Preferred method for preparing the composition of the present invention, for example, as described above, by adding lithium metal and chlorophenyl phosphine (chlorophenylphosphine) to the solvent, the lithium diphenyl phosphide in the solution of the solvent Reacting to form, wherein the solvent is characterized by producing a more stable solution than when the equivalent molar amount of tetrahydrofuran is used as the solvent. However, whatever amount of THF is used, the stability of the product is reduced.

The reaction is carried out at a temperature of 30 ° C to 80 ° C.

In a preferred embodiment, an initiator is added to the solution to enhance the formulation of diphenylphosphide. The initiator is preferably 1,2-dibromoethane.

DETAILED DESCRIPTION OF THE INVENTION

The diphenylphosphide solution of the present invention provides improved stability compared to a solution where the solvent is THF. Although 2MeTHF shows improved results when used as a solvent, any kind of organic solvent that provides improved overall stability can be used.

Preferred solvents are C ₁ -C ₅ compounds, with compounds of the form comprising oxygen or of which oxygen replaces at least one carbon. For example, as in the case of ethers, when oxygen substitutes for one carbon atom, it is preferred that at least two carbon atoms (as in the case of dimethyl ether) are present. Like furan, ethers are the preferred solvent group. The ether preferably comprises an ether having one or two ether units (-COC-), more preferably ethers in linear chain form. Diethyl ether, methylethyl ether and dipropyl ether are most preferred, and therefore compounds having 6 carbons are also preferred.

Preferred furan is 2MeTHF, which produces improved results compared to the corresponding THF without the methyl group.

Lithium metal is preferably pure lithium with little impurities, but more preferably comprises sodium in the range of 0.001 to 2% by weight, 1.0 to 1.5% by weight. The lithium metal may be provided in any form, but lithium metal particles are particularly preferred and usually have dispersions in organic liquids having an average particle size in the range of 1 to 150 microns, preferably 20 to 30 microns ( as a dispersion. If lithium metal is provided as a dispersion in a dispersant such as, for example, heptane, the dispersant can be removed, for example, by washing with a selected solvent to produce LDPP.

As the initiator, p-chlorodiphenyphosphine, which is a starting material, and any initiator that increases the initial reaction rate for converting lithium into lithium diphenylphosphide can be used.

In a preferred embodiment, the lithium, the solvent and the p-chlorodiphenylphosphine are added together and at a temperature higher than 30 ° C. to 80 ° C., preferably 30 ° C. to 40 ° C., or 40 ° C. to 80 ° C. The reaction takes place. The temperature is preferably below 50 ° C. because the product can decompose at or above this temperature.

The reactants may be mixed in any order, but it is preferred to add the lithium metal to the solvent before adding p-chlorodiphenylphosphine.

The reaction should proceed for a suitable time, prior to terminating the reaction, preferably for 1 minute to 10 hours, more preferably 20 minutes to 5 hours.

The product, lithium diphenylphosphide, can be recovered by any suitable means, for example by filtration. The lower the temperature, the longer the time required for filtration.

Preferred embodiments of the product and method of the present invention are described in detail in the following examples.

The solution of the present invention can be used to prepare enhanced and stable lithium diphenylphosphide formulations using solvents other than THF.

1 shows the DSC of LDPP in the DEM according to Example 38,
[0011] Figures 2 to 12 show the NMR spectra for the various embodiments,
[0012] FIGS. 13 to 36 is a lithium diphenyl phosphide photo stability of the sample,
37 shows the instrument used for titration of samples prepared according to the above examples.

Example  One

sample:

Lithium (technical grade metal from New Johnsonville, Chemetall Forte) stored in heptane (containing about 1% sodium as an impurity in metal with an average particle size of 20 to 30 microns) was redispersed and washed with hexane and Dried. The dried dispersed metal was mixed with mineral oil at a ratio of 1: 0.5 wt / wt and stored in a glovebox. Adding mineral oil to the lithium dispersion prevented the dried metal from scattering in the air in the glovebox. No additional sodium was added to the metal above that contained.

Commercially available p-chlorodiphenyphosphine from Aldrich (St. Louis, MO) (cat # C39601, 98%) was used as purchased.

Solvents tested include tetrahydrofuran (for comparison), diethyl ether and 2MeTHF. Prior to drying the solvent, the solvents were distilled on sodium metal. Other solvents were dried with molecular sieves or tested for moisture content before use. No purification was done before use.

Device:

Unless otherwise stated, all reactions mentioned were carried out in glass round bottom flasks and stirred with Teflon coated stir bars. All reactions were maintained in a constant pressure argon atmosphere maintained using a mineral oil bubbler. For less reaction (70 mL), the chlorodiphenylphosphine was added to a flask equipped with a syringe inserted with a long stainless steel needle.

For larger reactions (700 mL), the chlorodiphenylphosphine was added via a pressure equalizing addition funnel and the addition rate was changed to maintain the correct reaction temperature.

If necessary, the reaction was cooled to maintain 40 ° C. or lower. The temperature was measured with a glass thermometer. The small scale reaction was filtered through a glass frit filter (25-50 μm) and the larger reaction was filtered through a stainless steel filtration housing (3 inches) with a polypropylene filter cloth. All filters used Eagle-Picher Celatom FW-12 filter aids as filter bed.

NMR spectra were obtained from Varian 400MR using deuterated benzene as solvent, and the proton spectra referred to tetramethylsilane. The phosphorus containing spectrum was not calibrated (ie there is no internal standard to set ppm units).

DEM undergarment Example  reaction:

Amount of sample used in the experiment:

Lithium: 9.57 g (1.38 mol)

Chlorodiphenylphosphine: 126.22 g (0.572 mol)

Diethoxymethane: 489.12 g

A 1 liter flask equipped with a stir bar was charged with lithium (as described above, 1: 0.5 in mineral oil). The flask was equipped with a thermometer and an addition funnel. DEM was added and stirring was started. Approximately 10% (10 mL) of starting material was added to the flask. After 3 hours the temperature was raised to 21 ° C. and further addition was started. As needed, the temperature was maintained at 30 ° C ± 2 ° C by cooling. Additional addition was made for 80 minutes. NMR spectra were obtained after 1.5 hours, indicating that the reaction was not complete, so the solution was stirred overnight. The next morning, the reaction was terminated. The solution was then filtered to recover lithium diphenylphosphine, and then the filter residue was washed with 16.442 g of DEM. 601.96 g of a clean brown solution was taken and some samples were used for analysis (activity: 17.91%, yield: 98.09%).

Table 1 (see below) is a list of the solvents tested and the yields obtained. The reaction for preparing lithium diphenylphosphide was carried out at a temperature in the range of 30 ° C. to 80 ° C. The data shows that performing the reaction at temperatures below 40 ° C. improves yield and reduces filtration time, which is a preferred embodiment of the present invention. When the reaction was carried out at 30 ° C.-40 ° C., the filtration time was only 30-60 minutes, whereas a filtration time of approximately 3 hours was required when the reaction was carried out at higher temperatures. From the differential scanning calorimetry (DSC) diagram (FIG. 1), one can observe that the product starts to decompose at approximately 50 ° C.

On small scale (70 mL) the initiation of the reaction took 10-20 minutes. However, on larger scale (700 mL) the initiation of the reaction could take up to 3 hours.

If adding the starting material solution of lithium diphenylphosphide to the flask, it can be seen that the reaction is initiated quickly, although this is a preferred embodiment, but not essential to the practice of the present invention.

In Example 37 (4.2 gm), 1,2-dibromoethane was also added and the large scale scale experiment (700 mL) showed that the time required for initiation was reduced to approximately 1 hour.

The evolution of the reaction was monitored by both temperature and NMR. When the reaction was initiated, it was found that the reaction started as the color of the solution changed to green with an increase in temperature. To check the evolution of the reaction, NMR samples were obtained and the peaks at the aromatic sites were compared (FIGS. 10 and 11).

The stability of the product was tested at 20 ° C. and 35 ° C. of a controlled temperature incubator under an inert static pressure argon atmosphere (see Table 2-Table 9). Samples were placed in 2 ounce vials with Teflon stoppers and stored at this temperature for a period of 4 weeks. Example 28 showed that the amount of starting material remaining in the solution at the end of the reaction was greater than the usual amount (the ratio of product to starting material is 4: 1 compared to 4: 0.3, which is the usual ratio). ). By a 4-week stability test, the sample formed and developed a film on the wall of the vial. The film was not found in any other samples.

Data for Examples 1-42 Example Li (g) CDP (g) Li / CDP Solvent form Solvent (g) Temperature (℃) activation(%) yield(%) One 0.91 13.282 1.09 THF 60.81 40 9.2 60.23 2 0.94 13.203 1.13 THF 61.45 50 15.04 93.65 3 0.933 13.291 1.12 THF 61.29 49 13.16 86.91 4 0.91 13.344 1.08 THF 60.26 56 13.21 83.89 5 1.01 13.419 1.20 THF 59.78 65 14.28 90.84 6 0.647 9.105 1.13 THF 59.99 56 11.14 99.78 7 7.233 99.66 1.15 THF 498.4 62 13.9 94.75 8 7.4 100.08 1.18 THF 503.81 62 14.06 96.79 9 1.62 22.867 1.13 THF 61.48 60 21.58 92.36 10 2.19 30.244 1.15 THF 50.36 67 29.27 88.02 11 0.907 NA THF / hexane 8.78 / 51.40 55 na na 12 0.94 13.408 1.11 Dibutyl ether 53.27 64 9.02 48.43 13 0.953 13.169 1.15 DEM 59.98 65 14.9 93.26 14 0.94 13.046 1.15 DEM 57.91 70 14.81 85.94 15 0.947 13.179 1.14 DEM 51.7 50 16.58 90.95 16 0.94 13.079 1.14 DEM 52.72 52 16.36 92.21 17 0.93 13.097 1.13 DEM 52.89 68 15.76 88.12 18 0.93 13.313 1.11 MTBE 52.26 48 nr nr 19 0.927 13.163 1.12 2MeTHF 52.66 51 15.8 89.35 20 0.92 13.171 1.11 DME 52.19 50 10.41 53 21 0.913 Isopropyl ether 51.94 nr Nr 22 0.933 13.234 1.12 DMM 50.78 42 14.5 73.47 23 0.913 13.363 1.09 ether 53.85 34 14.25 75.35 24 0.94 13.082 1.14 DME 53.15 50 13.32 75.93 25 0.94 13.204 1.1316 TEOF 51.48 51 12.84 68.59 26 0.92 13.17 1.1104 DEM 51.7 52 16.32 89.44 27 0.92 13.315 1.0983 ether 52.31 34 17.32 89.92 28 8.733 124.74 1.1128 DEM 479.384 60 15.53 78.71 29 8.72 121.69 1.139 DEM 469.1 60 17.44 92.4 30 9.47 122.73 1.2265 2MeTHF 466.69 80 15.26 76.6 31 9.827 122.93 1.2707 DEM 475.56 78 16.47 83.63 32 0.92 13.44 1.0881 DEM 51.89 31 16.76 89.87 33 1.04 13.179 1.2544 DEM 51.87 31 17.2 94.16 34 9.57 126.22 1.2052 DEM 489.12 31 17.91 98.09 35 1.01 13.33 1.2044 DEM 51.25 31 17.82 95.42 36 9.693 122.62 1.2565 DEM 471.24 31 17.19 94.74 37 9.51 124.19 1.2172 DEM 493.97 31 17.34 94.97 38 1.013 13.219 1.2181 DEM 51.18 41 17.96 96.56 39 19.17 250.47 1.2166 DEM 720.68 31 22.35 98.25 40 19.17 259.78 1.1729 DEM 721.94 30 21.1 91.14 41 19.06 251.2 1.2061 DEM 717.43 31 22.01 99.52 42 11.94 155.81 1.2181 DEM 434.45 32 20.9 93.84

nr = no reaction

TEOF = triethylorthoformate

THF = tetrahydrofuran

DEM = diethoxymethane

DMM = dimethoxymethane

2MeTHF = 2 methyltetrahydrofuran

Ether = diethylether

NA = In Example 11, NA means that the product is formed but crystallized out of solution rather than forming a dispersion.

The following is the methodology used to calculate the data in Table 1:

sec- Butanolo  Lithium diphenyl phosphide by titration ( Lithium diphenylphosphide  ; Determination of active base in LDPP)

General All glassware should be oven dried and cleaned with argon. Xylene and 2-butanol were dried over activated molecular sieves before use. Titration was performed under an inert atmosphere of dry argon.

Proper configuration (Titration set - up ) . A three necked round bottom flask, dried and cleaned with argon, was sealed with a septum and kept in an argon atmosphere with an argon line. The dried burette was cooled, sealed with a septum, and its end was introduced into the round bottom flask through a hole formed in the septum (see FIG. 37). To maintain pressure equilibrium during the titration, an argon-filled glass syringe was connected through a septum at the top of the burette.

Solvent Preparation and Drying . In order to transfer 20 ml of xylene to the round bottom flask, an argon washed syringe was used. An argon washed syringe was used to transfer 0.5 ml of 0.05 M 1,10-phenanthroline indicator in xylene to the flask. Another washed syringe with a needle was used to add a few drops of the sample to the solution in the flask until it turned dark purple. Samples in flasks were titrated with 0.5 M sec-butanol in xylene titrant until the endpoint of the indicator was reached. The volume was measured with a burette as the starting volume.

Titration . In order to obtain a 2 ml sample, an argon rinse syringe with a needle inserted was used and the mass of the _sample was recorded as closest to 0.0001 gram as wgt _sample . The sample was injected into a titration flask and titrated to the indicator endpoint. The final volume was recorded and the volume used during the titration was calculated. The volume of titrant used was calculated as V _titrant in liters.

Active base concentration

stability

The stability of several solutions of LDPP in various solvents was tested. The results are shown in the table below. Samples without temperature were run at 20 ° C. and the analysis was performed on the same sample. Samples showing temperature have a plurality of samples from the same batch. All data are expressed in weight percent.

Stability of LDPP in Tetrahydrofuran LDPP in THF
Example 19 Day 0 week 1 week 2 week 4 20 ℃ 35 ℃ 20 ℃ 35 ℃ 20 ℃ 35 ℃ activation 11.08 10.1 8.8 9.23 4.58 7.62 One all 11.97 12 12 12.02 12.04 12.01 12.04

Stability of LDPP in Diethoxymethane LDPP in DEM
Example 13 Day 0 week 1 week 2 week 4 activation 14.9 14.56 14.54 14.52 all 15.5 15.56 15.66 15.65

Stability of LDPP in 2-methyltetrahydrofuran LDPP in 2MeTHF
Example 19 Day 0 week 1 week 2 week 4 activation 15.8 15.5 15.48 15.42 all 16.06 16.17 16.21 16.24

Stability of LDPP in Ether LDPP in ether
Example 23 Day 0 week 1 week 2 week 4 activation 14.28 14.06 14.04 14.04 all 15.54 15.56 15.54 15.55

Stability of LDPP in Triethylorthoformate LDPP in triethyl orthoformate
Example 25 Day 0 week 1 week 2 week 4 activation 12.84 10.96 8.98 6.34 all 13.03 13.04 12.985 12.99

Stability of LDPP in Diethoxymethane LDPP in DEM
Example 28 Day 0 week 1 week 2 week 4 20 ℃ 35 ℃ 20 ℃ 35 ℃ 20 ℃ 35 ℃ activation 15.53 15.54 15.44 15.52 15.25 15.48 14.88 all 17.1 17.11 17.13 17.08 17.1 17.03 16.96

Stability of LDPP in Diethoxymethane LDPP in DEM
Example 29 Day 0 week 1 week 2 week 4 20 ℃ 35 ℃ 20 ℃ 35 ℃ 20 ℃ 35 ℃ activation 17.44 17.42 17.36 17.41 17.26 17.39 17.12 all 18.03 18.02 18.01 18.06 18.09 18.04 18.06

2 Stability of LDPP in MeTHF LDPP in 2MeTHF
Example 30 Day 0 week 1 week 2 week 4 20 ℃ 35 ℃ 20 ℃ 35 ℃ 20 ℃ 35 ℃ activation 15.26 15.18 14.80 15.16 14.59 15.13 14.39 all 15.64 15.66 15.66 15.62 15.66 15.38 15.64

The results indicate that improved and stable lithium diphenylphosphide formulations can be prepared using solvents other than THF. Except for triethylorthoformate, all solvents used in the experiments showed improved results compared to THF formulations.

All documents cited above are incorporated by reference in their entirety for all purposes.

Claims (16)

Lithium diphenylphosphide and the solution composition comprises a solvent comprising at least one of methyltetrahydrofuran, dimethoxymethane or diethoxymethane, the solvent being tetrahydro A solution that produces a more stable solution than when it is tetrahydrofuran. delete delete delete The solution of claim 1 wherein the methyltetrahydrofuran is 2-methyltetrahydrofuran. delete The solution of claim 1 further comprising an initiator. The solution of claim 7, wherein the initiator is 1,2-dibromoethane. Adding chlorodiphehnyphosphine with lithium metal in the solvent;
Reacting to form lithium diphenylphosphide in a solution of the solvent,
Wherein the solvent comprises at least one of methyltetrahydrofuran, dimethoxymethane or diethoxymethane and produces a more stable solution when an equivalent molar amount of tetrahydrofuran is used as the solvent. The method of claim 9, wherein the reaction is carried out at a temperature of 30 ℃ to 80 ℃. 10. The method of claim 9, further comprising adding an initiator. 12. The method of claim 11, wherein the initiator is 1,2-dibromoethane. delete delete delete delete

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